AutologousCD22 Chimeric Antigen Receptor (CAR)T Cells in w/Recurrent/Refractory B Cell Lymphomas
Phase Ib Clinical Trial of Autologous CD22 Chimeric Antigen Receptor (CAR) T Cells in Adults With Recurrent or Refractory B Cell Lymphomas
2 other identifiers
interventional
148
1 country
1
Brief Summary
This is a non-randomized clinical trial to evaluate the safety and efficacy of CD22CART administered after lymphodepleting chemotherapy in adults with relapsed / refractory B Cell Lymphomas. All evaluable participants will be followed for overall survival (OS), progression free survival (PFS), and duration of response (DOR). An evaluable participant is one who completes leukapheresis, lymphodepleting chemotherapy and CART infusion.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2024
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 8, 2024
CompletedStudy Start
First participant enrolled
March 29, 2024
CompletedFirst Posted
Study publicly available on registry
April 1, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2031
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 1, 2031
August 7, 2025
August 1, 2025
7 years
March 8, 2024
August 4, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Determine the manufacturing feasibility of CD22 CART by assessing the target dose level and release specifications in each disease cohort.
Rate of successful manufacture of CD22CART cells at the target dose level that meet required release specifications in Cohort 1, Cohort 2, and Cohort 3.
6 years
Maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D)
Establish the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of CD22CART cells in 3 cohorts of adults with relapsed/refractory B Cell lymphoma.
6 years
Determine the overall response rate (ORR) in adults with follicular lymphoma (FL) and mantle cell lymphoma (MCL)
Assess the ORR at 3 months post CD22 CART infusion as defined by the disease specific response criteria for Cohort 1 (FL) and Cohort 2 (MCL)
3 months CD22 CART infusion
Secondary Outcomes (4)
Evaluate Progression Free Survival (PFS)
6 years
Evaluate Overall Survival (OS)
6 years
Evaluate Duration of Response (DOR)
6 years
Assess the response rate in adults with relapsed/refractory Hairy cell leukemia (HCL), Lymphoplasmacytic lymphoma (Waldenstrom macroglobulemia) (WM), Burkitt lymphoma (BL), and Marginal Zone lymphoma (MZL).
3 months post CD22
Study Arms (4)
Cohort 1: Follicular lymphoma (FL)
EXPERIMENTAL18-34 participants with FL will be administered the RP2D of CD22CART
Cohort 2: Mantle cell lymphoma (MCL)
EXPERIMENTAL12-32 participants with MCL will be administered the RP2D of CD22CART.
Cohort 3: Other lymphomas
EXPERIMENTALUp to 30 participants with no more than 10 of any one type, including: Hairy cell leukemia, Lymphoplasmacytic lymphoma (Waldenstrom macroglobulinemia), Burkitt lymphoma, and Marginal zone lymphoma.
Cohort 4: Relapsed/refractory large B cell lymphoma (LBCL)
EXPERIMENTAL14 - 19 participants will be administered the RP2D of CD22 CART
Interventions
Dosing and Administration Participants will be hospitalized to receive treatment with CD22CART, if not previously hospitalized, and will remain hospitalized for approximately 5 to 7 (±2) days. Patients may be discharged once all AEs have resolved to Grade 1 or better, or at the discretion of the treating physician. Participants may be discharged with non critical and clinically stable or slowly improving toxicities (e.g., renal insufficiency, cytopenias) even if \> Grade 1, if deemed appropriate by the investigator.
Eligibility Criteria
You may qualify if:
- Disease: Must have histologically confirmed disease as defined by WHO 2016\[117\] of one of the following:
- Follicular Lymphoma, grade 1-3a
- Relapsed or refractory disease after at least 2 lines of systemic therapy. Prior therapy must have included an anti-CD20 monoclonal antibody combined with systemic therapy (single-agent anti- CD20 antibody does not count as line of therapy for eligibility nor does local radiation). Anti-CD20 antibody is not required for participants with CD20 negative disease. A systemic therapy includes, but is not limited to: Bendamustine, CHOP, CVP, CART therapy, lenalidomide, or platinum-based chemotherapy.
- Relapsed or progressive disease within 24 months of initiation of the initial course of chemotherapy (also known as progression of disease within 24 months POD24). Initial treatment must have included an anti-CD20 monoclonal antibody (unless CD20 negative) plus either Bendamustine, CHOP or CVP (R-Chemo). Must have completed 3 or more cycles of R-Chemo. Progression is measured from the initial day of treatment of the first cycle of R-Chemo. In the case of those who received anti-CD20 monoclonal antibody monotherapy previously and then received R-Chemo are also eligible if they are POD24, and progression is measured from the initial day of treatment of the first cycle of R-Chemo and not from the initial day of anti-CD20 monoclonal antibody monotherapy.
- Mantle Cell Lymphoma 1. Relapsed or refractory disease after at least 2 lines of systemic therapy. Prior therapy must have included an anti-CD20 monoclonal antibody combined with systemic therapy. Anti-CD20 antibody is not required for participants with CD20negative disease.
- \. Participants who have received an anti-CD20 monoclonal antibody in combination with chemotherapy AND a Bruton's Tyrosine Kinase inhibitor as a single line of therapy are also eligible.
- Hairy cell leukemia (HCL)
- Diagnosis of HCL and require treatment as defined by having HCL-related anemia (hemoglobin \<11 g/dL), thrombocytopenia (platelets\<100 x 10\^9 /L), or neutropenia (absolute neutrophil count below 1.5 x 10\^9/L); symptomatic splenomegaly or adenopathy; or other constitutional symptoms directly related to HCL;
- Must have progressed or been refractory to 2 lines of therapy including a purine nucleoside analog.
- Lymphoplasmacytic lymphoma (Waldenstrom macroglobulinemia (WM)) - participants must meet all eligibility criteria listed
- \. Must have confirmed diagnosis of WM based on Second International Workshop on WM 2. Relapsed or refractory disease after 2 or more lines of therapy
- \. Prior therapies must include a i. BTKi ii. either chemotherapy and/or proteasome inhibitor 3. Requires treatment based on the recommendations from the Second International Workshop on WM 4. Requires the presence of serum IgM that is at least 2 times the upper limit of normal 5. Patients cannot require plasmapheresis for symptomatic hyperviscosity. 6. Patients cannot have symptomatic central nervous system involvement (Bing-Neel syndrome) that would prevent the assessment of neurotoxicity 7. Patients cannot have transformed to large B cell lymphoma Burkitt lymphoma (BL)
- \. Relapsed or refractory to front line chemoimmunotherapy; Participants with high-grade B-cell lymphoma with MYC and BCL2 and/orBCL6 rearrangements will be excluded.
- Marginal zone lymphoma (MZL)
- \. Must have received 2 prior lines of therapy including rituximab in combination with chemotherapy or a BTKi
- +28 more criteria
You may not qualify if:
- Presence rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy.
- \. History or current other malignancies, apart from non-melanoma skin cancer, low-grade untreated prostate cancer under observation, or carcinoma in situ, unless disease free for at least 3 years, or in remission 1-2 years and Principal Investigator assesses other malignancy as unlikely to return within 1 year or interfere with CAR T cell safety
- \. Presence of active fungal, bacterial, viral or other infection requiring intravenous antimicrobials. Simple UTI or uncomplicated bacterial pharyngitis is permitted if responding to active treatment.
- \. Ongoing HIV, HBV, or HCV infection. History of HBV or HCV is permitted if viral load is undetectable by qPCR and/or nucleic acid testing.
- \. Active cerebrovascular ischemic/hemorrhage, dementia, cerebellar disease, or autoimmune disease with CNS involvement that in investigator's judgement impair ability to evaluate neurotoxicity.
- \. History of MI, cardiac angioplasty or stenting, unstable angina or other clinically significant cardiac disease within 12 months of enrollment.
- \. Severe, immediate hypersensitivity reaction attributed to compounds of similar chemical or biologic composition to any agents used in study.
- \. Is pregnant or breastfeeding.
- \. Active primary immunodeficiency or history of autoimmune disease (e.g. Crohn's disease, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years.
- \. May NOT, in investigator's judgment, have any medical condition likely to interfere with assessment of safety or efficacy, or be likely to complete all protocol-required visits and procedures.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Stanford Universitylead
- The Leukemia and Lymphoma Societycollaborator
Study Sites (1)
Stanford University
Palo Alto, California, 94304, United States
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Matthew Frank, MD, PhD
Stanford University
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 8, 2024
First Posted
April 1, 2024
Study Start
March 29, 2024
Primary Completion (Estimated)
April 1, 2031
Study Completion (Estimated)
April 1, 2031
Last Updated
August 7, 2025
Record last verified: 2025-08